Lengthy consent form still needs adjustments

Smallpox study consent has significant flaws

The 10-page human subjects consent form proposed for the Dryvax vaccination study of children, ages 2 to 5, has a number of flaws, according to the IRBs and experts who have reviewed the study proposal and consent form.

"The consent form should provide more complete information and avoid language that minimizes the potential risks from this vaccine," says Neal A. Halsey, MD, professor of international health and pediatrics at Johns Hopkins University in Baltimore and the director of the Institute for Vaccine Safety of the Bloomberg School of Public Health, also at Johns Hopkins. Halsey’s comments about the study and consent form were obtained by the Department of Health and Human Services (DHHS) as part of a public review of the potential study.

The consent form includes a couple of pages of risks and discomforts that could result from the vaccine and one-third of a page describing benefits that may reasonably be expected. "The risk of death from smallpox vaccination for children in this age group was estimated to be two for every 1 million first vaccinations," the consent form states. 

Under benefits to the child, the consent form lists potential protection against the smallpox virus, in addition to:

  • "Your child will continue to receive routine and sick child care from their regular pediatrician or nurse practitioner."
  • "There will be no costs to you or your child for participation in the study."

Rosemary B. Quigley, JD, MPH, one of the 10 experts asked by DHHS to review the protocol and consent form, says in her letter to DHHS that this statement should be removed because there could be costs, such as withdrawing the child from daycare and paying for baby-sitting or from the loss of work pay.

Under benefits to humanity, the consent form states:

  • "Participation in this study may provide benefits to society in the search for a method for giving Dryvax vaccine safely and effectively so that the greatest number of individuals may receive protection against smallpox."
  • "These benefits may not happen and unexpected side effects may also develop."

The consent form also states that if a child participant is injured because of the research, emergency medical care will be available. "The care will not necessarily be free of charge. Financial compensation for any injury from this research is not available," the consent form adds.

Halsey’s letter to DHHS notes that the consent form makes no mention of the fact that one-third of adults who received Dryvax had sufficient discomfort and inability to use their arm so that they missed school or work. "On the consent form there is a notation of central nervous system infection’ at the bottom of page six, but there is no mention that severe persistent neurologic sequelae are common in children who develop post-vaccinial encephalitis," he wrote. "There is no known effective therapy for post-vaccinial encephalitis."

Parents and guardians should be shown photographs of some of the more common skin rashes that occur in children, as part of the consent process, Halsey adds. Further, he points out that the "Dear Parent" letter was inaccurate in stating that the routine Dryvax immunization was stopped in 1971 because the world was declared free of smallpox. "Routine immunization against smallpox was stopped because of the serious adverse events associated with smallpox vaccine and the very low risk of exposure to smallpox," Halsey states. "The last case of naturally occurring smallpox occurred in 1977, and the world was not declared free of smallpox until 1980."

The IRB at Kaiser Permanente Southern California, which was one of three IRBs to review the protocol, suggested that the consent form contain an additional exclusion of children who have a propensity to bite.

The Cincinnati Children’s Hospital Medical Center IRB, which like the Kaiser IRB has reviewed and approved the protocol, suggested that investigators use a more formal screening process to determine how rational parents are and to rule out significant psychological issues, according to the IRB’s minutes from a review meeting held in July.

"You have to make sure you are dealing with someone who will make a rational choice and also make sure you are dealing with a family who can control the possible exposure of contacts," the minutes read. "If you are dealing with a family that deals in chaos, this may not be possible."